rs2070534

Positions:

• chr21-43755489-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003681.5(PDXK):​c.760-209G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 585,418 control chromosomes in the GnomAD database, including 31,346 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.33 (8095 hom., cov: 34)
  • Exomes 𝑓: 0.32 (23251 hom.)
• Consequence: PDXK NM_003681.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.19

Genes affected

PDXK (HGNC:8819): (pyridoxal kinase) The protein encoded by this gene phosphorylates vitamin B6, a step required for the conversion of vitamin B6 to pyridoxal-5-phosphate, an important cofactor in intermediary metabolism. The encoded protein is cytoplasmic and probably acts as a homodimer. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 21-43755489-G-A is Benign according to our data. Variant chr21-43755489-G-A is described in ClinVar as [Benign]. Clinvar id is 1175405.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDXK	NM_003681.5	c.760-209G>A		intron_variant		ENST00000291565.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDXK	ENST00000291565.9	c.760-209G>A		intron_variant		1	NM_003681.5	P1

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49464 AN: 152092 Hom.: 8090 Cov.: 34

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.351

GnomAD4 exome AF: 0.324 AC: 140226 AN: 433208 Hom.: 23251 Cov.: 3 AF XY: 0.324 AC XY: 73793 AN XY: 228108

Gnomad4 AFR exome AF: 0.318

Gnomad4 AMR exome AF: 0.385

Gnomad4 ASJ exome AF: 0.343

Gnomad4 EAS exome AF: 0.451

Gnomad4 SAS exome AF: 0.340

Gnomad4 FIN exome AF: 0.281

Gnomad4 NFE exome AF: 0.306

Gnomad4 OTH exome AF: 0.326

GnomAD4 genome AF: 0.325 AC: 49499 AN: 152210 Hom.: 8095 Cov.: 34 AF XY: 0.327 AC XY: 24347 AN XY: 74416

Gnomad4 AFR AF: 0.322

Gnomad4 AMR AF: 0.379

Gnomad4 ASJ AF: 0.329

Gnomad4 EAS AF: 0.487

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.302

Gnomad4 OTH AF: 0.354

Alfa AF: 0.300 Hom.: 885

Bravo AF: 0.336

Asia WGS AF: 0.382 AC: 1332 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.91
DANN	Benign	0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2070534; hg19: chr21-45175370;